Type I IFN Signaling Is Crucial for Host Resistance against Different Species of Pathogenic Bacteria

Abstract

It is known that host cells can produce type I IFNs (IFN-αβ) after exposure to conserved bacterial products, but the functional consequences of such responses on the outcome of bacterial infections are incompletely understood. We show in this study that IFN-αβ signaling is crucial for host defenses against different bacteria, including group B streptococci (GBS), pneumococci, and Escherichia coli. In response to GBS challenge, most mice lacking either the IFN-αβR or IFN-β died from unrestrained bacteremia, whereas all wild-type controls survived. The effect of IFN-αβR deficiency was marked, with mortality surpassing that seen in IFN-γR-deficient mice. Animals lacking both IFN-αβR and IFN-γR displayed additive lethality, suggesting that the two IFN types have complementary and nonredundant roles in host defenses. Increased production of IFN-αβ was detected in macrophages after exposure to GBS. Moreover, in the absence of IFN-αβ signaling, a marked reduction in macrophage production of IFN-γ, NO, and TNF-α was observed after stimulation with live bacteria or with purified LPS. Collectively, our data document a novel, fundamental function of IFN-αβ in boosting macrophage responses and host resistance against bacterial pathogens. These data may be useful to devise alternative strategies to treat bacterial infections.

Type I Interferons Mediate the Innate Cytokine Response to Recombinant Fowlpox Virus but Not the Induction of Plasmacytoid Dendritic Cell-Dependent Adaptive Immunity

“…When examining the role for IFNAR in IL-12 and TNF-␣ secretion, we observed that in both cases IFNAR and, by inference, type I IFNs were required for high- level secretion of these cytokines. This observation is supported by other studies which suggest that simultaneous activation of both STAT1 and NF-B is important in the priming of IL-12 production in DCs (54) and that TNF-␣ secretion can be influenced by type I IFN secretion (32). Finally IL-1␤, an important mediator in the inflammatory response and a downstream indicator of inflammasome activation (37), was produced exclusively in GM-CSF-expanded DCs although when cDCs were sorted and concentrated from FL-expanded cultures, they, too, were also able to produce IL-1␤, albeit at low levels.…”

Mast cells elicit proinflammatory but not type I interferon responses upon activation of TLRs by bacteria

“…Thus, any excesses or deregulation leading to an imbalance in these sets of responses may spell doom to the host. In this regard, although type I IFNs were found to play a protective role during some bacterial infections (16), recent findings suggest that strong type I IFN responses not only result in increased susceptibility to bacterial infections (10)(11)(12)(13)(14) but also are a central pathologic event in sepsis and other hyperinflammatory conditions associated with bacterial infections (2,15).…”

Recognition of yeast nucleic acids triggers a host‐protective type I interferon response

“…41: 1969-1979 Immunity to infection previously [14]. Primers and TaqMan MGB probes for the above cytokines have been described previously [14] and were purchased from Applied Biosystems. PCR conditions were as follows: 951C, 10 min; (951C, 15 s; 601C, 1 min) Â 40 cycles.…”

“…Real-time PCR data were normalized in each individual sample by the level of b-actin expression. Gene expression was measured by the comparative C T method (DDC T ) and was reported as the n-fold difference relative to the normalized expression of unstimulated samples [14]. …”